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Results for “Epilepsy, Generalized”

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PubMed1977

[The treatment of primary generalized epilepsies with dipropyl acetate (DPA)].

79 patients with primary generalized epilepsies have been treated with DPA in a medium dosage of 51 mg/kg bodyweight/day, range 14 to 125 mg/kg/day, for a medium time of 22 months, range 2 to 49 months. 51 children out of this group had been treated previously and were therapy resistant to other medications. 27 children got DPA for their first medication. 34 patients were treated with DPA as a single drug, 45 were treated in combination with other medications. Therapeutic success was found to be remarkable good in impulsive petit mal (n = 4, all patients without any more seizures), in absences (n = 52, complete success in 84%), and in primary generalized grand mal seizures with spike-waves in the EEG alone or in combination with petit mal (n = 30, 87% success). However, centrencephalic myoclonic-astatic seizures (n = 17, no more seizures in 35%) were influenced significantly less. Side effects were rarely seen, mostly they could be observed in those patients treated with DPA and another medication. Side effects never induced interruption of treatment with DPA.

Adolescent↗

PubMed2001

Generalized epilepsy with febrile seizures plus: further heterogeneity in a large family.

BACKGROUND: Generalized epilepsy with febrile seizures plus (GEFS(+)) is a recently described benign childhood-onset epileptic syndrome with autosomal dominant inheritance. The most common phenotypes are febrile seizures (FS) often with accessory afebrile generalized tonic-clonic seizures (GTCS, FS(+)). In about one third, additional seizure types occur, such as absences, myoclonic, or atonic seizures. So far, three mutations within genes encoding subunits of neuronal voltage-gated Na(+) channels have been found in GEFS(+) families, one in SCN1B (beta(1)-subunit) and two in SCN1A (alpha-subunit). METHODS: The authors examined the phenotypic variability of GEFS(+) in a five-generation German family with 18 affected individuals. Genetic linkage analysis was performed to exclude candidate loci. RESULTS: Inheritance was autosomal dominant with a penetrance of about 80%. A variety of epilepsy phenotypes occurred predominantly during childhood. Only four individuals showed the FS or FS(+) phenotype. The others presented with different combinations of GTCS, tonic seizures, atonic seizures, and absences, only in part associated with fever. The age at onset was 2.8 +/- 1.3 years. Interictal EEG recordings showed rare, 1- to 2-second-long generalized, irregular spike-and-wave discharges of 2.5 to 5 Hz in eight cases and additional focal parietal discharges in one case. Linkage analysis excluded the previously described loci on chromosomes 2q21-33 and 19q13. All other chromosomal regions containing known genes encoding neuronal Na(+) channel subunits on chromosomes 3p21-24, 11q23, and 12q13 and described loci for febrile convulsions on chromosomes 5q14-15, 8q13-21, and 19p13.3 were also excluded. CONCLUSION: These results indicate further clinical and genetic heterogeneity in GEFS(+).

Adult↗

PubMed2002

Failure to replicate an allelic association between an exon 8 polymorphism of the human alpha(1A) calcium channel gene and common syndromes of idiopathic generalized epilepsy.

The present replication study tested the validity of a previously reported allelic association between a single nucleotide polymorphism in exon 8 (SNP8) of the gene encoding the alpha(1A)-calcium channel subunit (CACNA1A) and common subtypes of idiopathic generalized epilepsy (IGE). Pyrosequencing was applied to assess the SNP8 genotypes in 354 unrelated German IGE probands, both parents of 118 IGE probands, and 186 healthy control subjects of German descent. Our population-based association analysis did not provide evidence for an allelic association of SNP8 with either IGE or two phenotypically more homogeneous IGE subtypes, consisting of either 139 probands with juvenile myoclonic epilepsy or 207 probands whose IGE started with typical absence seizures (P>0.72). In addition, the transmission disequilibrium test did not indicate a preferential transmission of SNP8 alleles in 97 informative parent-child transmissions (McNemar chi(2)=0.093, df=1, P=0.76). Accordingly, we failed to confirm previous evidence that genetic variation of the CACNA1A gene confers susceptibility to common IGE syndromes.

Alleles↗

PubMed1998

Unusual EEG pattern linked to chromosome 3p in a family with idiopathic generalized epilepsy.

OBJECTIVE: To map the gene causing an unusual EEG pattern of delta bursts that appears to segregate as an autosomal dominant trait in an Italian family. The EEG pattern was observed in four family members affected by idiopathic generalized epilepsy (IGE) and in six other clinically unaffected members. METHODS: All available family members underwent clinical and EEG examination. DNA samples were obtained and used to perform a whole-genome scan with 270 microsatellite markers. After the first linked marker was identified, 12 additional markers in the same chromosomal region were tested to confirm linkage and define a candidate interval. RESULTS: The gene responsible for the EEG trait was mapped to an 11-cM interval on the proximal short arm of chromosome 3 (3p14.2-p12.1). CONCLUSION: In this family, a characteristic EEG activity is due to the effect of a single gene on chromosome 3p. A gene encoding a Ca2+ channel subunit maps in the interval and is a potential candidate for the trait. The clinical expression of epilepsy in four family members may reflect the interaction of additional genes, though environmental or other factors cannot be excluded.

Chromosome Mapping↗

PubMed2003

Video-EEG evidence of lateralized clinical features in primary generalized epilepsy with tonic-clonic seizures.

BACKGROUND: Whether cortical or subcortical structures, specifically the thalamus, play the dominant role in generating primary generalized seizures has been the subject of long debate. Most experimental data implicate a hyperexcitable cortical generator of spike-and-wave activity, with the thalamus quickly recruited to sustain the generalized oscillations through a reverberating thalamocortical network. However, there is little clinical evidence to support the cortical generator hypothesis. We present video-EEG recordings of generalized tonic-clonic seizures in three patients with proven primary generalized epilepsy (PGE), all of whom showed a consistent pattern of lateralized seizure onset compatible with a focal frontal lobe generator. METHODS: Among 300 patients referred for video-EEG monitoring for intractable epilepsy, three were found to have PGE with tonic-clonic convulsions. All had a positive family history for epilepsy and no other epilepsy risk factors. Epilepsy onset was during adolescence (2/3) or childhood (1/3). Patients were taking 1-4 antiepileptic drugs (AEDs) at admission, none of which was valproic acid. RESULTS: Interictal EEG showed very active, bilaterally synchronous generalized spike-and-wave or polyspike-and-wave discharges between 2.5-4.5 Hz, maximal over the midfrontal structures symmetrically in all patients. Ictal EEG showed generalized rhythmic activity without lateralization at seizure onset. Surprisingly, in all 6 recorded tonic-clonic seizures there was a sustained (10-15 seconds), stereotyped, clinical lateralization at onset, which took the form of a tonic "fencing posture" in one patient (two seizures) and forced head/eye/torso version in two patients (four seizures). Two patients became seizure-free shortly after switching to valproate monotherapy. One patient refused valproate but has improved more than 90% with a change in AEDs to lamotrigine and phenobarbital (follow-up in all patients>18 months). CONCLUSIONS: Tonic-clonic seizures are presumed to be generalized from onset in patients with PGE. However, video-EEG monitoring in these patients is rarely performed and the actual clinical features of the seizures maybe underappreciated. The demonstration of sustained lateralization at onset in our patients, with features clinically indistinguishable from focal onset frontal lobe seizures, is compatible with the hypothesis of a focal region of cortical hyperexcitability situated in the frontal lobes of some patients with PGE. Whether this cortical generator is autonomous or "triggered" by ascending, possibly normal, thalamocortical volleys is unresolved.

Adult↗

PubMed2005

Distribution of spatial complexity of EEG in idiopathic generalized epilepsy and its change after chronic valproate therapy.

The objective of this study was to investigate the global and regional spatial synchrony of the EEG background activity, and to assess the effect of chronic valproate therapy on spatial synchrony. 15 idiopathic generalized epilepsy (IGE) patients were examined and compared to 16 normal controls. Resting EEG with 19 channels was investigated before and during chronic administration of valproate (VPA). Omega, a single-valued measure of spatial covariance complexity, was calculated to assess the degree of spatial synchrony of EEG. Furthermore, a new parameter was defined to characterize the distribution of spatial synchrony (Antero-Posterior Complexity Ratio, APCR). Global Omega complexity was significantly lower in IGE compared to controls, while regional complexity showed significant differences only in the anterior region: the IGE group showed lower complexity. APCR was significantly lower in IGE. VPA therapy (1) lowered the global complexity, (2) increased regional complexity in the anterior region, but decreased it in the posterior region, and (3) increased APCR. In IGE lower complexity, i.e. enhanced spatial synchrony, was found, especially in the anterior cortical area. VPA modified the distribution of spatial synchrony in IGE patients towards that of normal controls, although the effect is not identical with full normalization of cortical bioelectric activity. Whether the observed change of spatial synchrony distribution may reflect the normalizing effect of valproate on the brain state is worth further investigation.

Adolescent↗

PubMed2000

Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia.

Inactivation of the beta4 subunit of the calcium channel in the mouse neurological mutant lethargic results in a complex neurological disorder that includes absence epilepsy and ataxia. To determine the role of the calcium-channel beta4-subunit gene CACNB4 on chromosome 2q22-23 in related human disorders, we screened for mutations in small pedigrees with familial epilepsy and ataxia. The premature-termination mutation R482X was identified in a patient with juvenile myoclonic epilepsy. The R482X protein lacks the 38 C-terminal amino acids containing part of an interaction domain for the alpha1 subunit. The missense mutation C104F was identified both in a German family with generalized epilepsy and praxis-induced seizures and in a French Canadian family with episodic ataxia. These coding mutations were not detected in 255 unaffected control individuals (510 chromosomes), and they may be considered candidate disease mutations. The results of functional tests of the truncated protein R482X in Xenopus laevis oocytes demonstrated a small decrease in the fast time constant for inactivation of the cotransfected alpha1 subunit. Further studies will be required to evaluate the in vivo consequences of these mutations. We also describe eight noncoding single-nucleotide substitutions, two of which are present at polymorphic frequency, and a previously unrecognized first intron of CACNB4 that interrupts exon 1 at codon 21.

Amino Acid Sequence↗

PubMed1983

Primary generalized epilepsy and temporal lobe epilepsy: a psychological study using Rorschach tests.

Rorschach tests were performed on patients with primary generalized epilepsy (PGE) and on patients with temporal lobe epilepsy (TLE) combined with generalized tonic-clonic convulsions. Each group consisted of 20 cases and the two groups were matched as closely as possible. Patients with PGE were found to be characterized by variable responses, sensitivity, extroversion and undifferentiated tendencies. Patients with TLE are practical but inefficient and constricted in character. Cases not on medication displayed the same character types. On the basis of the above findings, speculation is made concerning the features of neurotic or psychotic PGE patients.

Adult↗

PubMed2001

Genetic variation of the human glycine receptor subunit genes GLRA3 and GLRB and susceptibility to idiopathic generalized epilepsies.

Alterations of glycine receptor alpha1 and beta subunit genes have been associated with hypertonic motor disorders in both mice and humans. Mutations in genes encoding other ligand- and voltage-gated ion channels have been identified in rare monogenic forms of idiopathic generalized epilepsies (IGE). We tested the hypothesis that allelic variants of the glycine receptor subunit genes, GLRA3 and GLRB, both localized on chromosome 4q, confer susceptibility to common subtypes of IGE. Mutation screening was carried out in index patients of 14 IGE families. No pathogenic mutation was found, but two intronic polymorphisms were detected in the GLRB gene, and four intronic, three exonic, and one 3'-UTR polymorphisms were identified for the GLRA3 gene. Subsequent screening for exonic and 3'-UTR polymorphisms in GLRA3 showed no statistical difference between a group of sporadic IGE patients (n = 104) and a control group (n = 141). The genotype frequencies for exonic and 3'-UTR polymorphisms in GLRA3 showed no statistically significant difference between IGE patients (n = 104) and an ethnically matched control group (n = 141). Thus, no association between IGE and alterations in GLRA3 or GLRB genes could be detected, indicating that both genes do not play a major causative role in the epileptogenesis of common IGE subtypes. Still, these novel single nucleotide polymorphisms may be useful markers for candidate gene analyses of other disorders.

Alleles↗

PubMed1998

Mapping, genomic structure, and polymorphisms of the human GABABR1 receptor gene: evaluation of its involvement in idiopathic generalized epilepsy.

Neurophysiological and pharmacological studies suggest a major role of the GABAB receptor in the epileptogenesis of absence seizures. The gene encoding the human GABABR1 receptor (GABABR1) has recently been mapped to human chromosome 6p21.3 by in situ hybridization, a region that harbors a susceptibility locus (EJM1) for idiopathic generalized epilepsy (IGE). We investigated the hypothesis that the GABABR1 gene (GABBR1) represents a candidate gene for EJM1 by: (1) defining the precise localization approximately 130 kilobases telomeric to the HLA-F locus, (2) by characterizing its genomic organization, and (3) by mutation screening of the entire coding region of GABBR1 in 18 German patients with juvenile myoclonic epilepsy (JME) who were derived from families with evidence for linkage to chromosome 6p21.3 (cumulative lod score Z=3.17 at HLA-DQ). The GABAB receptor gene consists of 22 translated exons. The two alternative transcripts, GABABR1a and GABABR1b, are derived from the same locus but they differ in their alternative 5'-exons. Mutation analyses in JME revealed several DNA sequence polymorphisms, two of which result in amino acid changes occurring in all IGE-affected members of two families. However, clinically unaffected relatives did carry the same variations, excluding these amino acid substitutions as the cause for IGE in these families.

Amino Acid Substitution↗

PubMed1999

Idiopathic generalized epilepsies with versive or circling seizures.

OBJECTIVES: To describe the electroclinical features of the idiopathic generalized epilepsies (IGEs) with versive or circling seizures. METHODS: Sixteen patients with versive or circling seizures and interictal electroclinical features of IGE were studied. Patients with insufficient clinical or imaging data, with a follow-up period less than 1 year or with partial seizures in addition to the versive or circling ones were excluded from the study. All patients underwent full interictal clinical and neurophysiological studies. The EEG patterns of 13 versive or circling seizures from 4 patients were also analyzed. RESULTS: A specific IGE syndrome was recognized in 9 out of the 16 patients (56%). More specific, 1 patient had childhood absence epilepsy (CAE), 4 had juvenile absence epilepsy (JAE), and 4 had juvenile myoclonic epilepsy (JME). No specific IGE syndrome was recognizable in the remaining 7 patients (44%). These 7 patients had a juvenile epileptic syndrome (mean age at onset of seizures was 15.7 years) characterized by versive or circling seizures followed or not by generalized tonic-clonic fits. Three main EEG patterns were identified during versive or circling seizures: 1) generalized spike-and-wave discharges at 3-4 cps; 2) generalized polyspike-and-wave discharges at 1 to 2.5 cps beginning with generalized fast activity at 12-14 cps, and 3) generalized spike-and-wave discharges at 3-4 cps intermingled with fast activity at 12-14 cps. Most patients had good response to treatment on a single drug regimen (mainly valproic acid). CONCLUSIONS: Versive or circling seizures may occur in the context of an IGE. Although many individuals share the features of different IGE syndromes including CAE, JAE and JME, a consistent number of patients, who show circling or versive seizures solely, remain without a specific syndromic diagnosis. When occurring in the context of IGE, circling or versive seizures do not worsen the prognosis.

Adolescent↗

PubMed2000

The voltage-gated sodium channel beta2-subunit gene and idiopathic generalized epilepsy.

Recent identification of ion channel gene mutations in Mendelian epilepsies suggests that genetically driven neuronal hyperexcitability plays an important role in epileptogenesis. In this study, we tested the hypothesis that genetic variation in the human SCN2B gene confers liability to common subtypes of idiopathic generalized epilepsies (IGE). A systematic search for mutations was performed in 92 IGE patients. We detected a novel single nucleotide polymorphism (SNP), however, allele frequencies did not differ between IGE patients and controls (chi2 = 0.19, df = 1, p = 0.744). Furthermore, a missense mutation in codon 209 (Asn209Pro) was identified in one patient, but was found to be absent in an affected sibling of the index patient. Thus, our results do not suggest a major role of the SCN2B gene in the etiology of common IGE subtypes.

Adult↗

PubMed1994

The effects of chronic treatment with a calcium channel antagonist on two types of generalized epilepsies in rats.

Although calcium antagonists possess antiepileptic properties in various models of epilepsy, their role after chronic administration and in models for generalized absence epilepsy has not been studied. Twenty-four male Wistar rats, aged 84-94 weeks, were chronically provided with EEG electrodes. Two groups received dietary nimodipine (860 ppm) for 14 and 21 weeks, respectively, while a control group received the same rat chow without nimodipine. The EEG was recorded for 3 h to establish the effects of nimodipine on spike-wave discharges. Next, 50 mg/kg pentylenetetrazol (PTZ) was injected to establish the effects on convulsive epilepsy, and the EEG was recorded for 30 min. All animals had spontaneous spike-wave discharges (SWD), but there were no differences between the three groups. However, chronic nimodipine treatment had a significant effect on PTZ-induced seizures: the group that had been treated with nimodipine for 21 weeks showed significantly more and longer-lasting seizures than the control group. The facilitating effects of chronically administered of nimodipine on PTZ-induced seizures are striking and opposite to those reported in the literature. In a second study, nimodipine was administered acutely, but no effects of nimodipine on PTZ-induced epilepsy could be detected. It can be concluded that chronic dietary administration of a calcium antagonist induces different effects on PTZ-induced seizures than acute administration in aged Wistar rats with spontaneous occurring SWD.

Animals↗

PubMed2002

Mild generalized epilepsy and developmental disorder associated with large inv dup(15).

PURPOSE: Several studies attempted to clarify the genotype-phenotype correlations in patients with inverted duplication of chromosome 15 [inv dup(15)], which is usually characterized by severe mental retardation and epilepsy in individuals with large duplications including the Prader-Willi/Angelman region. We report two patients with inv dup(15) who, in spite of a large duplication, had a mild phenotype including adult-onset epilepsy. This report may help to define the milder spectrum of the syndrome. METHODS: A 25-year-old girl with mild mental retardation had a 6-year history of absence seizures, with occasional head drop. Interictal EEG revealed diffuse spike-wave complexes. Epilepsy was well controlled by a combination of lamotrigine (LTG) and valproate (VPA). The other patient, a 27-year-old man with mild mental retardation, had a 5-year history of rare generalized tonic-clonic seizure during sleep, and frequent episodes of unresponsiveness, which appeared to be atypical absence seizures on video-EEG recordings. A combination of VPA and LTG led to a remarkable improvement, although no complete control. RESULTS: Molecular analysis revealed a large inv dup15 in both patients. CONCLUSIONS: The discrepancy between the mild phenotype and the severe chromosomal abnormality detected in these two patients further supports the notion that the site of breakpoint might be contributory to the inv dup(15) phenotype. Inv dup(15) should be considered in atypical cases of generalized epilepsy of adult onset without clear-cut etiology.

Adult↗

PubMed2003

Effects of topiramate in two models of genetically determined generalized epilepsy, the GAERS and the Audiogenic Wistar AS.

PURPOSE: The antiepileptic effects of topiramate (TPM) were assessed in two models of genetically determined generalized epilepsy. The model of nonconvulsive epilepsy used was a model of absence seizures, the GAERS (Genetic Absence Epilepsy Rat from Strasbourg); and the model of convulsive seizures was an audiogenic rat model, the Wistar Audiogenic Sensitive (AS) rat. METHODS: GAERS were equipped with four cortical electrodes over the frontoparietal cortex, and the duration of spike-and-wave discharges (SWDs) on the EEG was recorded for periods of 20 to 120 or 300 min. In Wistar AS, the occurrence of, latency to, and duration of one or two wild running episodes and tonic seizures were recorded. RESULTS: In the 16 GAERS studied, TPM (10, 30, and 60 mg/kg) dose-dependently reduced the expression of SWD that almost totally disappeared at the two highest doses between 40 and 120 min. SWD duration returned to control levels by 180 and 280 min after the injection of 30 and 60 mg/kg TPM, respectively. In Wistar AS, 10 mg/kg TPM induced the occurrence of a second running episode not present in control rats, indicative of a decrease in sensitivity of the rats to the stimulus and increased by 330% the latency to the tonic seizure that still occurred in the eight rats studied. At 30 and 60 mg/kg, the latency to wild running increased by 140%; the second running episode was suppressed in six and seven rats, respectively, whereas the tonic seizure occurred only in one of the eight rats studied at these two doses. CONCLUSIONS: These results support the broad spectrum of antiepileptic activity of TPM, confirming its efficacy in primary generalized seizures of both tonic-clonic and of the absence type.

Animals↗

PubMed1977

Treatment of generalized epilepsies of childhood and adolescence with sodium valproate ("epilim").

A total of 142 patients (84 per cent aged less than 20 years) with various forms of generalized epilepsy have been treated with sodium valproate alone or in combination with other drugs. The mean duration of symptoms was six years, and half the patients had daily seizures. Nine patients had typical absences, 33 had absences with automatisms, 28 had tonic-clonic seizures with or without photosensitivity, and 72 had various forms of myoclonic epilepsy. Dosage varied from 23 to 54mg/kg and twice-daily administration was usual. Estimation of serum levels did not assist in management. Fits ceased in 63 per cent of all cases and a further 18 per cent showed improvement greater than 50 per cent. Of the 69 with 3c/sec spike-and-wave discharges, 81 per cent became free from all fits, as did 77 percent of those with myoclonic jerks. Fits ceased in eight of the 32 patients with myoclonic astatic epilepsy and there was improvement greater than 50 per cent in a further eight patients. Other anticonvulsants were often withdrawn and always reduced. 21 patients received sodium valproate alone from the start of treatment and all other drugs were withdrawn in another 38. Sodium valproate alone controlled all fits in four children with absences, in 18 with absences with automatisms, 10 with tonic-clonic seizures and 22 with myoclonic epilepsy. Side-effects were rare, mild and often temporary. Potentiation of barbiturates and benzodiazepines occurred, especially clonazepam, which should be avoided. Many patients were more alert. Sodium valproate appears to be the drug of choice for epilepsies associated with generalized spike-and-wave discharges, myoclonic epilepsies or photosensitive epilepsies, and is of especial value in children and mentally retarded patients because it lacks sedating effects and often induces liveliness.

Adolescent↗

PubMed2004

Functional evaluation of human ClC-2 chloride channel mutations associated with idiopathic generalized epilepsies.

The ClC-2 Cl- channel has been postulated to play a role in the inhibitory GABA response in neurons or to participate in astrocyte-dependent extracellular electrolyte homeostasis. Three different mutations in the CLCN2 gene, encoding the voltage-dependent homodimeric ClC-2 channel, have been associated with idiopathic generalized epilepsy (IGE). We study their function in vitro by patch clamp and confocal microscopy in transiently transfected HEK-293 cells. A first mutation predicts a premature stop codon (M200fsX231). An altered splicing, due to an 11-bp deletion in intron 2 (IVS2-14del11), predicts exon 3 skipping (Delta74-117). A third is a missense mutation (G715E). M200fsX231 and Delta74-117 are nonfunctional and do not affect the function of the normal (wild type, WT) channel. Neither M200fsX231 nor Delta74-117 reach the plasma membrane. Concerning the IVS2-14del11 mutation, we find no difference in the proportion of exon-skipped to normally spliced mRNA using a minigene approach and, on this basis, predict no alteration in channel expression in affected individuals. G715E has voltage dependence and intracellular Cl- dependence indistinguishable from WT channels. ClC-2 channels are shown to be sensitive to intracellular replacement of ATP by AMP, which accelerates the opening and closing kinetics. This effect is diminished in the G715E mutant and not significant in WT+G715E coexpression. We do not know whether, in a situation of cellular ATP depletion, this might become pathological in individuals carrying the mutation. We postulate that loss of function mutation M200fsX231 of ClC-2 might contribute to the IGE phenotype through a haploinsufficiency mechanism.

Adenosine Monophosphate↗

PubMed1997

Possible association of a silent polymorphism in the neuronal nicotinic acetylcholine receptor subunit alpha4 with common idiopathic generalized epilepsies.

The alpha4 subunit gene of the neuronal nicotinic acetylcholine receptor (CHRNA4) has recently been identified as the first gene underlying an idiopathic partial epilepsy syndrome in human, autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE). CHRNA4 is located in the candidate region for benign familial neonatal convulsions and low-voltage EEG on chromosome 20q. In the present study, we examined the possible role of CHRNA4 in common subtypes of idiopathic generalized epilepsy (IGE), comprising childhood and juvenile absence epilepsy and juvenile myoclonic epilepsy (JME), by systematically screening the coding region of the gene for sequence variants. We present here a population-based association study testing the hypothesis that variants of the CHRNA4 gene confer genetic susceptibility to common subtypes of IGE. The missense mutation (Ser248Phe), associated with ADNFLE, and four silent polymorphisms in the CHRNA4 gene were genotyped in 103 IGE patients and 92 controls by polymerase chain reaction and subsequent restriction analysis. Without correction for multiple testing, the frequency of the T-allele of the silent CfoI bp595 polymorphism was increased in the entire group of IGE patients (f(T) = 0.085) compared to that in the controls (f(T) = 0.027). The allelic association was not restricted to any subgroup of IGE with either JME or idiopathic absence epilepsies. This result suggests that variation of the CHRNA4 gene, or so-far-undetected sequence variants near the CHRNA4 locus, confer susceptibility to the common IGE syndromes.

Alleles↗